• Journal of Life Science
• /
• v.33 no.9
• /
• pp.713-723
• /
• 2023

Lung cancer is a type of cancer that has the highest mortality rate. It is mainly classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Chemotherapy is used to treat lung cancer, but long-term treatment causes side effects and drug resistances. Curcumin is a bright yellow polyphenol extracted from the root of turmeric. It has biological activities, such as anti-oxidant, anti-cancer, and anti-inflammatory effects. In this study, we observed differential cell death in human lung cancer cells. Based on the results, curcumin at 10, 30, and 50 μM exhibited a dose-dependent inhibition on the cell survival of several lung cancer cells, with minor differential phenotypes. In addition, apoptosis, autophagy, and reactive oxygen species (ROS) regeneration were observed through flow cytometry. Curcumin dose-dependently increased these phenotypes in A549 (NSCLC) and DMS53 (SCLC), which were restored by corresponding inhibitors. Western blotting was performed to measure the level of expression of apoptosis- and autophagy-related proteins. The results indicate that Bax, PARP, pro-caspase-3, and Bcl-2 were dose-dependently regulated by curcumin, with seemingly higher Bax/Bcl-2 ratios in DMS53. In addition, autophagic proteins, p-AKT, p62, and LC3B, were dose-dependently regulated by curcumin. ROS inhibition by diphenyleneiodonium reduced the induction of apoptosis and autophagy generated by curcumin. Taken together, it is suggested that curcumin induces apoptosis and autophagy via ROS generation, leading to cell death, with minor differences between human lung cancer cells.

• Radiation Oncology Journal
• /
• v.25 no.1
• /
• pp.16-25
• /
• 2007

[ $\underline{Purpose}$ ]: Breast conserving surgery (BCS) followed by chemotherapy (CTx.) and radiation therapy (RT) is widely performed for the treatment of early breast cancer. This retrospective study was undertaken to evaluate our interim results in terms of failure patterns, survival and relative risk factors. $\underline{Materials\;and\;Methods}$: From January 1999 through December 2003, 129 patients diagnosed with invasive breast cancer and treated with BCS followed by RT were subject to retrospective review. The median age of the patients was 45 years (age distribution, $27{\sim}76$ years). The proportions of patients according to their tumor, nodes, and metastases (TNM) stage were 65 (50.4%) in stage I, 41 (31.7%) in stage IIa, 13 (10.1%) in stage IIb, 9 (7.0%) in stage III, and 1 patient (0.8%) in stage IIIc. For 32 patients (24.8%), axillary node metastasis was found after dissection. BCS consisted of quadrantectomy in 115 patients (89.1%) and lumpectomy in 14 patients (10.6%). Axillary node dissection at axillary level I and II was performed for 120 patients (93%). For 7 patients (5.4%), only sentinel node dissection was performed with BCS. For 2 patients (1.6%) axillary dissection of any type was not performed. Postoperative RT was given with 6 MV X-rays. A tumor dose of 50.4 Gy was delivered to the entire breast area using a tangential field with a wedge compensator. An aditional dose of $9{\sim}16\;Gy$ was given to the primary tumor bed areas with electron beams. In 30 patients (23.3%), RT was delivered to the supraclavicular node. Most patients had adjuvant CTx. with $4{\sim}6$ cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimens. The median follow-up period was 50 months (range: $17{\sim}93$ months). $\underline{Results}$: The actuarial 5 year survival rate (5Y-OSR) was 96.9%, and the 5 year disease free survival rate (5Y-DFSR) was 93.7%. Local recurrences were noted in 2 patients (true: 2, regional node: 1) as the first sign of recurrence at a mean time of 29.3 months after surgery. Five patients developed distant metastases as the first sign of recurrence at $6{\sim}33$ months (mean 21 months). Sites of distant metastatic sites were bone in 3 patients, liver in 1 patient and systemic lesions in 1 patient. Among the patients with distant metastatic sites, two patients died at 17 and 25 months during the follow-up period. According to stage, the 5Y-OSR was 95.5%, 100%, 84.6%, and 100% for stage I, IIa, IIb, and III respectively. The 5Y-DFSR was 96.8%, 92.7%, 76.9%, and 100% for stage I, IIa, IIb, and III respectively. Stage was the only risk factor for local recurrence based on univariate analysis. Ten stage III patients included in this analysis had a primary tumor size of less than 3 cm and had more than 4 axillary lymph node metastases. The 10 stage III patients received not only breast RT but also received posterior axillary boost RT to the supraclavicular node. During the median 53.3 months follow-up period, no any local or distant failure was found. Complications were asymptomatic radiation pneumonitis in 10 patients, symptomatic pneumonitis in 1 patient and lymphedema in 8 patients. $\underline{Conclusion}$: Although our follow up period is short, we had excellent local control and survival results and reaffirmed that BCS followed by RT and CTx. appears to be an adequate treatment method. These results also provide evidence that distant failure occurs earlier and more frequent as compared with local failure. Further studies and a longer follow-up period are needed to assess the effectiveness of BCS followed by RT for the patients with less than a 3 cm primary tumor and more than 4 axillary node metastases.

• Journal of Chest Surgery
• /
• v.39 no.2 s.259
• /
• pp.106-110
• /
• 2006

Background: Bronchioloalveolar carcinoma (BAC) is an uncommon primary malignancy of the lung, and it accounts for $2{\~}14\%$ of all pulmonary malignancies. According to World Health Organization (WHO) categorisation, BAC is a subtype of adenocarcinoma. The current definition of BAC includes the following: malignant neoplasms of the lung that have no evidence of extrathoracic primary adenocarcinoma, an absence of a central bronchogenic source, a peripheral parenchymal location, and neoplastic cells growing along the alveolar septa. Previous reports had demonstrated a better prognosis following surgery for patients affected by BAC than those affected by other type of non-small cell lung cancer (NSCLC). We aim to analyse Asan Medical Center experiences of BAC. Material and Method: Between 1990 and 2002, 31 patients were received operations for BAC. We analyse retrosepectively sex, age, disease location, preoperative clinical stage, postoperative pathologic stage & complications, survival according to medical record. Result: There were 12 men and 19 women, the average age was 61.09$\pm$10.63 ($31{\~}79$) years. Tumor locations were 7 in RUL, 1 in RML, 4 in RLL, 8 in LUL, 11 in LLL. Operations were 28 lobectomies, 2 pneumonectomies. Postoperative pathologic stage were 12 T1N0M0, 15 T2N0M0, 1 T1N1M0, 1 T1N2M0, 1 T2N2M0, 1 T1N0M1. Mortality were 4 cases ($12.9\%$) and there were no early mortality. Cancer free death was 1 cases, other 3 were cancer related deaths. All of them were affected by distal metastasis and received chemotherapy and each metastatic locations were right rib, brain, and both lung field. The average follow up periods were 50.87$\pm$24.77 months. The overall 3, 5-year survival rate among all patients was $97.1\%,\;83.7\%$, stage I patients overall 2, 5year survival rate was $96.3\%$. The overall disease free 1, 2, 5-year survival rate among all patients was $100\%,\;90\%,\;76\%$ and 2, 5-year survival rate in cases of stage I was $96.4\%,\;90.6\%$. 7 cases ($22.58\%$) were chemotherapies, 1 case ($3.22\%$) was radiation therapy, and 2 cases ($6.45\%$) were chemoradiation therapies. Metastatic locations were 3 cases in lung, 1 case in bone, 1 cases in brain. Conclusion: BAC has a favourable survival and low recurrence rate compare with reported other NSCLC after operative resections.

• Radiation Oncology Journal
• /
• v.18 no.4
• /
• pp.257-264
• /
• 2000

Purpose: For early stage non-small-cell lung cancer, surgical resection is the treatment of choice. But when the patients are not able to tolerate it because of medical problem and when refuse surgery, radiation therapy is considered an acceptable alternative. We report on the treatment results and the effect of achieving local control of primary tumors on survival end points, and analyze factors that may influence survival and local control. Materials and Method : We reviewed the medical records of 32 patients with medically inoperable non-small cell lung cancer treated at our institution from June, 1987 through June, 1997. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidate for surgical resection because of either patients refusal (4), old age (2), lung problem (21), chest wail invasion (3) and heart problems (3). In 8 patients, there were more than 2 problems. The median age of the patients was 68 years (ranging from 60 to 86 years). Histologic cell type included souamous (24), adenocarcinoma (6) and unclassiried squamous cell (2). The clinical stages of the patients were 71 in 5, 72 in 25, 73 in 2 patients. Initial tumor size was 3.0 cm in 11, between 3.0 cm and 5.0 cm in 13 and more than 5.0 cm in 8 patients. Ail patients had taken chest x-rays, chest CT, abdomen USG and bone scan. Radiotherapy was delivered using 6 MV or 10 MV linear accelerators. The doses of primary tumor were the ranging from 54.0 Gy to 68.8 Gy (median; 61.2 Gy). The duration of treatment was from 37 days through 64 days (median; 0.5 days) and there was no treatment interruption except 1 patient due to poor general status. In 12 patients, concomitant boost technique was used. There were no neoadjuvant or adjuvant treatments such as surgery or chemotherapy. The period of follow-up was ranging from 2 months through 93 months (median; 23 months). Survival was measured from the date radiation therapy was initiated. Results : The overall survival rate was 44.6$\%$ at 2 years and 24.5$\%$ at 5 years, with the median survival time of 23 months. of the 25 deaths, 7 patients died of intercurrent illness, and cause-specific survival rate was 61.0$\%$ at 2 years and 33.5$\%$ at 5 years. The disease-free survival rate was 38.9$\%$ at 2 years and 28.3$\%$ at 5 years. The local-relapse-free survival rate was 35.1$\%$, 28.1$\%$, respectively. On univariate analysis, tumor size was significant variable of overall survival (p=0.0015, 95$\%$ C.1.; 1.4814-5.2815), disease-free survival (P=0.0022, 95$\%$ C.1., 1.4707-5.7780) and local-relapse-free survival (p=0.0015, 95$\%$ C.1., 1.2910- 4.1197). 7 stage was significant variable of overall survival (p=0.0395, 95$\%$ C.1.; 1.1084-55.9112) and had borderline significance on disease-free survival (p=0.0649, 95$\%$ C.1.; 0.8888-50.7123) and local-relapse-free survival (p=0.0582, 95$\%$ C,1.; 0.9342-52.7755). On multivariate analysis, tumor size had borderline significance on overall survival (p=0.6919, 955 C.1., 0.9610-5.1277) and local-relapse-free survival ( p=0.0585, 95$\%$ C.1.; 0.9720-4.9657). Tumor size was also significant variable of disease-free survival (p=0.0317, 95% C.1.; 1.1028-8.4968). Conclusion : Radical radiotherapy is an effective treatment for small (71 or f3 cm) tumors and can be offered as alternative to surgery in elderly or infirmed patients. But when the size of tumor is larger than 5 cm, there were few long-term survivors treated with radiotherapy alone. The use of hypefractionated radiotherapy, endobronchial boost, radisensitizer and conformal or IMRT should be consider to improve the local control rate and disease-specific survival rate.

• Radiation Oncology Journal
• /
• v.26 no.4
• /
• pp.247-256
• /
• 2008

Purpose: The purpose of this study is to evaluate anal sphincter preservation rates, survival rates, and prognostic factors in patients with rectal cancer treated with preoperative chemoradiotherapy. Materials and Methods: One hundred fifty patients with pathologic confirmed rectal cancer and treated by preoperative chemoradiotherapy between January 1999 and June 2007. Of the 150 patients, the 82 who completed the scheduled chemoradiotherapy, received definitive surgery at our hospital, and did not have distant metastasis upon initial diagnosis were enrolled in this study. The radiation dose delivered to the whole pelvis ranged from 41.4 to 46.0 Gy (median 44.0 Gy) using daily fractions of $1.8{\sim}2.0\;Gy$ at 5 days per week and a boost dose to the primary tumor and high risk area up to a total of $43.2{\sim}54\;Gy$ (median 50.4 Gy). Sixty patients (80.5%) received 5-fluorouracil, leucovorin, and cisplatin, while 16 patients (19.5%) were administered 5-fluorouracil and leucovorin every 4 weeks concurrently during radiotherapy. Surgery was performed for 3 to 45 weeks (median 7 weeks) after completion of chemoradiotherapy. Results: The sphincter preservation rates for all patients were 73.2% (60/82). Of the 48 patients whose tumor was located at less than 5 cm away from the anal verge, 31 (64.6%) underwent sphincter-saving surgery. Moreover, of the 34 patients whose tumor was located at greater than or equal to 5 cm away from the anal verge, 29 (85.3%) were able to preserve their anal sphincter. A pathologic complete response was achieved in 14.6% (12/82) of all patients. The downstaging rates were 42.7% (35/82) for the T stage, 75.5% (37/49) for the N stage, and 67.1% (55/82) for the overall stages. The median follow-up period was 38 months (range $11{\sim}107$ months). The overall 5-year survival, disease-free survival, and locoregional control rates were 67.4%, 58.9% and 84.4%, respectively. The 5-year overall survival rates based on the pathologic stage were 100% for stage 0 (n=12), 59.1% for stage I (n=16), 78.6% for stage II (n=30), 36.9% for stage III (n=23), and one patient with pathologic stage IV was alive for 43 months (p=0.02). The 5-year disease-free survival rates were 77.8% for stage 0, 63.6% for stage I, 58.9% for stage II, 51.1% for stage III, and 0% for stage IV (p<0.001). The 5-year locoregional control rates were 88.9% for stage 0, 93.8% for stage I, 91.1% for stage II, 68.2% for stage III, and one patient with pathologic stage IV was alive without local recurrence (p=0.01). The results of a multivariate analysis with age (${\leq}55$ vs. >55), clinical stage (I+II vs. III), radiotherapy to surgery interval (${\leq}6$ weeks vs. >6 weeks), operation type (sphincter preservation vs. no preservation), pathologic T stage, pathologic N stage, pathologic overall stage (0 vs. I+II vs. III+IV), and pathologic response (complete vs. non-CR), only age and pathologic N stage were significant predictors of overall survival, pathologic overall stage for disease-free survival, and pathologic N stage for locoregional control rates, respectively. Recurrence was observed in 25 patients (local recurrence in 10 patients, distant metastasis in 13 patients, and both in 2 patients). Acute hematologic toxicity ($\geq$grade 3) during chemoradiotherapy was observed in 2 patients, while skin toxicity was observed in 1 patient. Complications developing within 60 days after surgery and required admission or surgical intervention, were observed in 11 patients: anastomotic leakage in 5 patients, pelvic abscess in 2 patients, and others in 4 patients. Conclusion: Preoperative chemoradiotherapy was an effective modality to achieve downstaging and sphincter preservation in rectal cancer cases with a relatively low toxicity. Pathologic N stage was a statistically significant prognostic factor for survival and locoregional control and so, more intensified postoperative adjuvant chemotherapy should be considered in these patients.